tbuckley/cabot-search huggingface dataset:
A prospective, open-label, randomized, controlled trial of radiofrequency ablation versus stereotactic body radiation therapy for recurrent small hepatocellular carcinoma.
Authors: Yaojun Zhang, Mian Xi, Minshan Chen, Li Xu, Shi-Liang Liu, Mengzhong Liu
Journal: Journal of Clinical Oncology (2023)

4096 Background: Effective treatments are urgently needed to improve the prognosis of patients with recurrent hepatocellular carcinoma (HCC). Previous studies demonstrated that both radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) were promising therapies for recurrent small HCC. This trial was designed to compare the efficacy and safety of RFA versus SBRT in patients with recurrent small HCC. Methods: This is a prospective, open label, randomized controlled trial, in which patients aged between 18 and 75 years with recurrent small HCC (occurred more than 3 months after hepatectomy or RFA, a solitary HCC ≤5.0 cm in diameter without vascular invasion or extrahepatic metastasis), KPS score ≥90, Child-Pugh score ≤6, adequate organ function, and estimated life expectancy ≥6 months were considered eligible. All patients were assigned 1:1 to RFA or SBRT group, and stratification was performed according to tumor size (≤ 2.0 cm or 2.1-5.0 cm). The primary endpoint was 2-year local progression-free survival. Secondary endpoints were progression-free survival, locoregional control, overall survival, and safety. Results: A total of 170 patients were recruited during August 2019 to May 2022 (83 in RFA arm and 87 in SBRT arm). In the ITT population, median age was 56 (range, 33-75) and 15 were female. Baseline characteristics were well balanced between treatment arms. Adverse events occurred in RFA and SBRT were mainly grade 1 or grade 2 in severity, and were gastrointestinal and constitutional symptoms, or abnormal laboratory investigations. The most common adverse events were bilirubin increase（14.6%）and AST increase (13.3%) in RFA group vs ALT increase (20.0%) and AST increase (15.3%) in SBRT group. No Grade 3-4 adverse events or mortality were noted. Late adverse events were hardly observed after 3 months. The follow-up of survival data is ongoing. Conclusions: Both RFA and SBRT are tolerable and safe for patients with recurrent small HCC. This randomized controlled trial will report the survival outcomes in 2024, which will make an important contribution in clinical decision-making for recurrent small HCC. Clinical trial information: NCT04047173 .
A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab.
Authors: Anne M. Noonan, Saira Farid, Patrick Schnell, Danielle Trunzo, Pannaga G. Malalur, Ning Jin, Ashish Manne, Laith I. Abushahin, Shafia Rahman, John L. Hays, Rifat T. Elkhatib, Arjun Mittra, Sameek Roychowdhury, Maryam B. Lustberg, Alex Sparreboom, Shuiying Hu
Journal: Journal of Clinical Oncology (2023)

e15613 Background: Neurotoxicity is one of the most significant and disabling side effects of oxaliplatin (OX) and frequently limits the amount of OX that can be used. OX uptake by organic cation transporter 2 (OCT2) into mouse and rat dorsal root ganglia is a prerequisite for OX-induced peripheral neuropathy (OIPN). Preclinical data in rat and mouse models from our group showed that by inhibiting YES1, pre-treatment with dasatinib (D) inactivated OCT2 and prevented acute and chronic OIPN. A phase I trial is ongoing investigating addition of D prior to OX to prevent OIPN. Methods: This is a Bayesian Phase 1b dose-finding study with adaptive dose selection using efficacy-toxicity trade-offs in patients (pts) with GI cancers who are candidates for mFOLFOX6 ± bevacizumab [NCT04164069]. Pts received chemotherapy on day 1 and 15 schedule, every 28 days. D was administered at one of 2 dose levels – 100mg or 140mg PO, given 24 hours and 30 mins prior to OX on C1D14, C1D15 respectively and repeated on C1D28 and C2D1. During cycle 1, pharmacokinetic and pharmacodynamic data was obtained at baseline, during, and up to 24 hours after D or OX administration. Recommended Phase 2 dose (RP2D) was defined as the lowest intermittent dose of D that increases serum biomarkers of OCT2, including methylnicotinamide (NMN) and creatinine, by ≥2-fold without influencing the clearance of oxaliplatin by ≥20%, toxicity profile was evaluated based on CTCAE v. 5.0. Results: 11 pts were screened. 5 pts enrolled in cohort 1 (D 100 mg) and 2 in cohort 2 (D 140 mg). In this preliminary analysis, 5 patients were evaluated for efficacy biomarkers and 4 pts were evaluated for both efficacy biomarkers and toxicity. There were no DLTs observed in either cohort. 3/5 pts had ≥2-fold increase in AUC of NMN, and 4/5 pts had ≥2-fold increase in AUC of creatinine. 4/5 pts had ≤20% change in the clearance of OX. Conclusions: Addition of D 140 mg to traditional FOLFOX regimen was safe and resulted in increasing levels of biomarkers as indication of inhibition of OCT2 in comparison to baseline for the majority of pts enrolled. Enrollment and analysis are ongoing at D 140mg dose to confirm the RP2D to prevent OPIN in a future randomized phase II study. Clinical trial information: NCT04164069 . [Table: see text]
Comparison of T cell infiltration in hepatocellular carcinoma between whole exome and transcriptome sequencing data.
Authors: Xing Lv, Wei Dong, Zunyi Zhang, Jian Li, Wenqiang Wang, Linfeng Dong, Zuoquan Yang, Yanqing Zhou, Shuhua Zhao, Shifu Chen, Erlei Zhang
Journal: Journal of Clinical Oncology (2023)

e16226 Background: Immunotherapy is one of the most promising therapeutics for hepatocellular carcinoma (HCC), and the immune infiltration status in tumors could be used as a biomarker for immunotherapy. However, evaluation of immune infiltration is usually based on RNA-Seq (transcriptome sequencing), which is limited in clinical practice due to the difficulty of handling RNA. On the other hand, WES (whole exome sequencing) is frequently performed to detect tumor mutations in cancer clinic. Therefore, we try to compare T cell infiltration in hepatocellular carcinoma obtained from WES data and RNA-Seq data, evaluate the potential of T cell infiltration from WES data as a biomarker for immunotherapy. Besides, we also evaluated the association of T cell fraction obtained from WES data and other clinical information. Methods: Seventy pairs of HCC tumor and matched normal tissue samples underwent both WES and RNA-Seq. T cell ExTRECT score and mcpCounter score were used to represent the immune infiltration status, and they were generated from WES data and RNA-Seq data respectively. Tumor mutational burden (TMB) score and some characteristics (tumor size, blood pressure, etc.) were also calculated for correlation analysis. Results: T cell ExTRECT score was positively correlated with mcpCounter score (Spearman correlation coefficient: 0.54). While TMB score showed no correlation with T cell ExTRECT score (Spearman correlation coefficient: -0.06) and mcpCounter score (Spearman correlation coefficient: -0.09). Besides, T cell ExTRECT score was negatively associated with main tumor size (Spearman correlation coefficient: -0.38) and High Blood Pressure (Spearman correlation coefficient: -0.37). Conclusions: These results suggest that T cell ExTRECT score obtained from WES and mcpCounter score generated by RNA-seq data is highly correlated, and neither of them is associated with TMB score. T cell ExTRECT score could be used to evaluate immune infiltration in hepatocellular carcinoma, and may serve as a biomarker for immunotherapy regardless of TMB score. Further investigation is still needed to evaluate the clinical outcome of immunotherapy for hepatocellular carcinoma with T cell ExTRECT score.
Comprehensive analysis of the mutational status of early colon cancer: Real world data from the AIO ColoPredict registry study.
Authors: Doreen Maria Gisder, Sarah Wisser, Celine Lugnier, Jens Christmann, Kraeft Anna-Lena, Inke Sabine Feder, Iris Tischoff, Christian Teschendorf, Heuer Vera, Bülent Sargin, Stepahn Hollerbach, Christof Lamberti, Andrea Tannapfel, Anke C. Reinacher-Schick
Journal: Journal of Clinical Oncology (2023)

e15535 Background: The comprehensive analysis of the mutational status of colon cancer (CC) may identify targetable alterations also in early stages. This may open up potential beneficial treatment choices, e.g. immunotherapy in microsatellite instable (MSI) tumors. So far, there is few data regarding the distribution of molecular alterations in CC in a real world setting in Germany. Methods: We analyzed clinical and molecular data from our Colopredict Plus (CPP) registry trial including CC patients (pts.) stage I-III. Samples were tested for MS status by immunohistochemistry and for gene mutations (MT) using a 71 gene panel comprised for CC. Molecular data was correlated with clinicopathologic parameters. Disease free Survival (DFS) was estimated by the Kaplan-Meier method. Results: Data from 2746 pts. was included. Female: 1476/2746 (53,8 %), median age: 72 yrs (range: 22-100 yrs), right sided tumor: 1607/2746 (58,5 %), stage distribution I/II/III/NA: 414 (15,1 %)/1198 (43,6 %)/1076 (39,2 %)/58 (2,1 %). MSI/MSS: 544(19,8%)/2202/ (80,2%). A KRAS mutation was observed in 846/2746 (30,8 %). The most frequent hotspot MT were codon 12 KRAS MT with p.G12D (27%), p.G12V (19%), p.G12A (6%), and p.G12C (6%) followed by codon 13 MT with p.G13D (18%). The subtypes p.G12D, p.G12V, and p.Q61K were significantly more frequent in the right colon. BRAF MT was seen in 560/2746 (20,4%). Observed rare MT were: POLE (76/2746 (2,8 %), PTEN 188/2746 (6,8 %), and EGFR (21/2746; 0,8%). MSI CC were more frequent in the right colon and associated with BRAF MT (346/560; 61,8 %), and also MT in BRCA1 (35/53; 66 %), BRCA2 (119/171; 69,6 %), POLE (45/76 (59,2 %), PTEN 107/188 (56,9 %), and EGFR (18/21, 85,7%). In contrast, TP53 MT (1223/2746 (44,5 %)) were associated with MSS (1090/2746 (49,5 %)). 3 yrs DFS in MSI BRAF WT vs. MSS BRAF MT pts. was 0,75 (0,67 – 0,81 vs 0,52 (0,36 – 0,65) (p =0,11). DFS did not differ in specific KRAS MT variants. Conclusions: We here show a comprehensive analysis of genetic alterations in early CC in a prospective real world cohort. As expected, MSI was correlated with female sex, right sided primary tumor and BRAF MT. Interestingly, we also found a strong correlation of BRCA1 MT, BRCA2 MT, EGFR MT, POLE MT, and PTEN MT with presence of MSI while MSS was associated with TP53 MT. Broad molecular characterization of early CC may help individualize treatment strategies in the future.
Racial and ethnic representation in large B-cell lymphoma trials and real-world databases.
Authors: Javier Munoz, Alex Mutebi, Tongsheng Wang, Guihua Zhang, Junhua Yu, Jing He, Anindit Chibber, Rajesh Kamalakar, Monika P. Jun, Kelechi Adejumo, Shibing Yang, Anupama Kalsekar
Journal: Journal of Clinical Oncology (2023)

e19530 Background: In large B-cell lymphoma (LBCL) trials, racial and ethnic representation is difficult to determine due to underreporting in some regions, or because some patients may not provide data. It is difficult to understand the full extent of any underrepresentation of specific races or ethnicities in these trials relative to the prevalence of LBCL in clinical practice. The objective of this study was to characterize racial and ethnic representation in LBCL real-world databases and recently published LBCL studies. Methods: Analyses of the distribution of different racial and ethnic categories were conducted across 6 real-world clinical practice databases from the United States (US): SEER-Medicare, COTA, Medicare, Optum Market Clarity, Optum CDM, and ConcertAI RWD. In addition, a targeted review of recently published studies in patients with LBCL was conducted to identify reported race and ethnicity distributions. Distributions were described using counts and percentages for each race (Asian, Black, White, and other/unknown/not reported) and ethnicity (Hispanic, non-Hispanic, and other/unknown/not reported) category. Results: Patients with LBCL from the databases included: COTA (N=5848), SEER-Medicare (N=102,548), Medicare (N=136,466), Optum Market Clarity (N=19,649), Optum CDM (N=22,175), and ConcertAI (N=1828). Race and ethnicity distributions are reported in the table. Across databases, Asian (2–6%) and Black (5–8%) races were substantially lower than White race (69–88%). Across various lines of therapy, distributions were similar: 3–5% Asian, 3–5% Black, and 78–82% White. Hispanic ethnicity (5–22%) was substantially lower than non-Hispanic ethnicity (70–91%). In the targeted review, 14 publications of LBCL therapies were identified; of these, 10 did not report racial/ethnic composition. In 4 publications (Salles et al, 2020; Sehn et al, 2020; Bannerji et al, 2022; and a real-world study by Shenoy et al, 2011), Asian, Black, White, and other/unknown/not reported represented 2–13%, 0–7%, 71–89%, and 1–11%, respectively. Conclusions: Information on racial and ethnic distributions in LBCL studies is underreported, particularly in global trials. If this information was reported and reflective of LBCL in clinical practice in the US, the numbers of Asian and Black patients would be low at ≤8%, and most patients would be expected to be White and non-Hispanic. [Table: see text]
Primary retroperitoneal lymph node dissection (RPLND) in seminoma stage IIA-IIC ≤3cm: Combined results of the SWENOTECA (Swedish Norwegian Testicular Cancer Group) and Cologne.
Authors: Torgrim Tandstad, Anders Kjellman, Bjarte Almås, Anna Grenabo Bergdahl, Gabriella Elisabeth Cohn-Cedermark, Axel Gerdtsson, Ingrid Glimelius, Dag L. Halvorsen, Hege Sagstuen Sagstuen Haugnes, Annika Hedlund, Asa Karlsdottir, Signe Melsen Larsen, Helene F. S. Negaard, David Pfister, Olof Stahl, Anna Thor, Rolf Wahlquist, Axel Heidenreich, Pia Paffenholz, Felix Seelemeyer
Journal: Journal of Clinical Oncology (2023)

Background: Chemotherapy or radiotherapy have been standard treatment for stage II seminomas with excellent survival but are associated with significant long-term treatment-related toxicities. Several prospective trials have shown primary retroperitoneal lymph node dissection (RPLND) to be an effective and safe alternative. The current SWENOTECA treatment program recommends primary RPLND in seminoma stage IIA to IIB ≤ 3 cm with 1-2 metastatic nodes as the standard treatment modality. We present preliminary results combined with data from Cologne. Methods: Within SWENOTECA, RPLND is centralized to 5 hospitals and Cologne is a tertiary centre for patients recruited from different parts of Germany. Both patients with recurrence after initial stage I disease and patients with primary stage IIA and IIB at diagnosis were included. We collected information on operation time, bleeding, peri- and postoperative complications. We also analyzed histologic outcome and whether adjuvant chemotherapy was given. We followed the patients for any recurrence of disease. Results: We have included 94 patients operated from May 2018 to November 2022. The number of operations per site varied from 4 to 28. The mean age of patients at time of RPLND was 41.8 years (range 21-79). Overall, 54 patients had recurrence after initial stage I disease and 40 patients had primary stage IIA/IIB disease at diagnosis (one missing data). At time of RPLND 62 patients had IIA-disease and 31 stage IIB-disease (one missing data). The histology from RPLND showed seminoma in 83 patients, benign/necrosis in eight patients, vital non-seminomatous GCT in one patient, teratoma only in one patient and lymphoma in one patient. Mean number of resected nodes was 19, and mean number of positive nodes were 1.5. Twenty-six patients (28%) were operated with robotic laparoscopic technique. Ten patients (10.6%) had a Clavien-Dindo postoperative complication &gt; 2. Twenty-three of the patients were given adjuvant oncological treatment after RPLND, most of them one course of BEP. The patients have been followed for in median 18 months (range 2-59). Nine patients (9.6 %) have had recurrences, all but one in the first year after RPLND. Conclusions: Our early results of primary RPLND of seminomas IIA-IIB ≤ 3 cm are promising. Longer follow-up is required to ensure this as a safe treatment option.
Early experience with nivolumab, gemcitabine, and lenvatinib for fibrolamellar hepatocellular carcinoma.
Authors: Paul Kent, Jordan C Tasse, Erik Schadde, Tom Kato, Abhinav Humar, Oliver M Fisher, Matthew Dixon, Tom Stockwell, Albert Cornelius, Thomas Kim, Jessica Ellison
Journal: Journal of Clinical Oncology (2023)

4076 Background: Fibrolamellar Carcinoma (FLC) is a rare deadly form of liver cancer affecting adolescents and young adults (AYA), presenting at an advanced stage, with up to 80% relapse, and no proven systemic therapies. Effective systemic therapies could convert patients to resectable or prolong progression free survival (PFS) and overall survival. Because of reported successes with nivolumab + lenvatinib (LEN) and of Gemcitabine (GEM) + LEN, and the potential synergy of GEM with NIV through elimination of myeloid suppressor cells in the tumor microenvironment, we offered NIV+LEN+GEN (NLG) to relapsed/refractory FLC patients ineligible for clinical trials. Our objective is to describe our initial experience using NLG in high risk AYA FLC patients. Methods: We reviewed the records of all FLC patients discussed at the FibroFighters National Tumor Board who received NLG. Results: Twenty-five patients (10F,15M), median age 20 (7-56), all stage IV, received a total of 322 cycles of NLG (median 11 cycles/patient,19 neoadjuvant, 1 adjuvant, 4 both). The median number of relapses, prior systemic therapies, and surgeries were 2(0-6), 3(0-6), and 2(0-7) respectively. Most patients had failed NIV+LEN (n = 8) or GEM+LEN (n = 7) prior to starting NGL. The 17 patients with at least one evaluation had a mean follow up of 10 months (3-23) and 18 cycles (6-38) of NGL with the best response by RECIST 1.1 of CR(1), PR(6), SD(10), and PD(0), for an objective response rate (PR+CR) of 41% and disease control rate (CR+PR+SD) of 100%, and estimated best volume response median of -20% (-89%,+10%). There have not yet been any progressions. Three of the 7 who were too soon for imaging, have had resolution of ascites. The PFS and Overall Survival at 6, 9, and 12 months are: 1.0/1.0, 0.82/0.82, 0.67/0.67. Two of 17 with carcinomatosis have no evidence of disease on PET and MRI after 10 cycles. Twenty-two of 24 are continuing NGL. Nine of 16 unresectable patients became surgical candidates, of these 4 showed &gt; 50% necrosis histologically at surgery. 13 of 17 showed necrosis on imaging. Eleven of 16 are currently in their longest PFS since diagnosis. Sixteen patients had serial tumor-informed circulating DNA (Signatera) during therapy: Five became negative (0.0 mean tumor molecules/ml plasma), and overall mean drop was -27% (-93%, +111%). No patients have stopped therapy. The most common toxicities were hypertension and fatigue in 25% and 20% respectively, grade 1 or 2. There have been no grade 3 or 4 toxicities to date. Conclusions: Our retrospective experience with NGL for FLC offers another potential systemic option for patients who are not surgical candidates or with multiple relapses. NGL was well tolerated and provided excellent disease control to patients with few options. Prospective trials are needed.
Disparities in pancreatic cancer among Asian-Pacific Islander and American Indian-Alaskan Native populations.
Authors: Jennifer Cullen, Tharun Rao, Weichuan Dong, Holly Hartman, Siran Koroukian
Journal: Journal of Clinical Oncology (2023)

e16275 Background: Pancreatic cancer (PanCan) is the third deadliest cancer in the United States, causing 8.2% of all U.S. cancer deaths. A steady rise in incidence rates has been observed nationally, with striking variation by geographic region and across race/ethnicity. Several studies have demonstrated a disproportionate burden of PanCan incidence on non-Hispanic Black (NHB) as compared to non-Hispanic White (NHW) populations. Yet little attention has been given to the burden of disease on Asian-Pacific Islander (API) and American Indian-Alaskan Native (AI/AN) populations. Additionally, there are limited data on disparities in PanCan incidence by U.S. geographical region. This study investigates age-adjusted incidence rates and annual percent change in PanCan incidence over a 20-year period, emphasizing burden of disease among API and AI/AN persons as well as by U.S. geographic region. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End-Results (SEER) database of 22 registries was used to study newly diagnosed pancreatic cancer cases (ICD-O-3/WHO 2008) for the period 2000-2019. Incidence rates and annual percent change were age-adjusted to the 2000 U.S. standard population and calculated per 100,000 persons using SEER*Stat software. Results: The overall age-adjusted PanCan incidence rates, from lowest to highest, for AI/AN, API, NHW and NHB populations were 6.6, 9.6, 12.5 and 15.3, respectively (per 100,000 persons). When examining each registry separately, two notable outliers were observed in the state of Hawaii where API and AI/AN persons had incidence rates of 13.4 and 24.5 per 100,000 persons, respectively. For all racial/ethnic groups, except AI/AN, the annual percent change in PanCan incidence significantly rose from 2000-2019, with increases of 0.9, 0.6 and 0.3 percent per year for NHW, API and NHB persons, respectively (p &lt; 0.05). Conclusions: A striking observation in this study was the unusually high PanCan incidence rates among API and AI/AN persons in the state of Hawaii, as compared to national rates. Moreover, a significant increase in annual percent change in PanCan incidence was observed over the study period for all racial/ethnic groups, except AI/AN. A key strength of this analysis is the examination of a large, population-based database over an extended time period. The SEER regions examined cover approximately 48% of the U.S. population and intentionally balance on racial/ethnic composition of the U.S. However, the database does not capture cancer incidence data from all U.S. states. Furthermore, this study did not examine sub-categories of API and AI/AN persons, which are groupings that may be heterogeneous with respect to disease burden over time and across U.S. regions. Future efforts will include refining the analysis into more granular racial/ethnic groups and exploring incidence rates among API and AI/AN subgroups in Hawaii.